Combination HIV Prevention: Now is the Time

April 25, 2013

Chris Beyrer MD, MPHJohns Hopkins Bloomberg School of Public Health

Combination HIV prevention

Strategic, simultaneous use of different classes of prevention: biomedical, behavioral, social/structural

Operates on multiple levels (individual, relationship, community, social), to respond to the specific needs of particular communities and modes of HIV transmission

Efficient use of resources through prioritizing, partnership, and engagement of affected communities

The CDC Continuum of HIV Care - 2011

80%

62%

41%36%

28%

Greenberg, CROI 2013

HIV treatment reduces incidence at community levels

Global HIV prevalence of HIV in MSM compared with regional adult prevalence in 2011

Source: Beyrer, Baral, van Griensven, Goodreau, Chariyalertsak, Wirtz, Brookmeyer, The Lancet, 2012

Map of HIV prevalence among female sex workers in low-income and middle-income countries, 2007-2011

Pooled OR for HIV infection among FSW compared to other reproductive age women: 13.49 (95% CI 10.04-18.12)

Map of HIV prevalence among transgender women, 2000-2011

Pooled OR for HIV infection among TGW compared to other reproductive people: 48.8 (95% CI 31.2-76.3)

Combinations for Key Populations

Strategic, simultaneous use of different classes of prevention: biomedical, behavioral, social/structural

Targeted to the drivers of HIV: granular, specific, acceptable, scalable

Implemented in partnership, with real engagement of affected communities

Effect of different intervention combinations and yearly recruitment rates on HIV incidence after 5 years

Degenhardt, et al. Prevention of HIV infection for people who inject drugs. Lancet 2010.

Scaling up Combination HIV Interventions when force of infection is great: Nairobi, Kenya IDUs. (Strathdee, et al,

Lancet 2010)

MP3: MODEL EVALUATED IMPACT OF COMBINATION HIV PREVENTION FOR MSM IN SOUTH AFRICA

KEY MODEL CHARACTERISTICS• Agent based stochastic model (micro-simulation)• Calibrated to peri-urban South Africa MSM• Sexual mixing networks of main, regular & casual partners• Accounts for increased transmission with UAIs• Accounts for heterogeneities in sexual behaviors (predominantly receptive, predominantly insertive, versatile) frequency of HIV testing (high, low, never testers)• Accounts for impact of ART on risk of acquisition and transmission• Accounts for variability in acceptance and adherence rates to PREP

MODEL OUTPUTCumulative incident infections over 5 years AIMS:• Reduce UAIs• Increase ART coverage for tested HIV infected persons (<350 CD4)• Provide PREP for high risk persons (># partners or in sero-discordant couples)• Increase HIV testing

The Sibanye MP3 Project (NIAID R01-AI094575) PI: Patrick Sullivan

Conclusions

• Combination prevention is already a reality

• Refinement needed—research will be key

• Combinations for key populations will need to be targeted, informed by epidemiology, specific to be effective

The Present and The Future of HIV Prevention:Voluntary Medical Male CircumcisionApril 25, 2013

Three randomized control trials (RCTs) demonstrated that adult VMMC reduces men’s risk of HIV acquisition by 60 percent

Follow-up up to five or six years post-trial indicated that this protective effect was durable and even increased over time.

VMMC is a one-time, short procedure that confers a lifetime of reduced HIV infection risk for heterosexual men. VMMC also reduces the risk for human papillomavirus (HPV), cervical cancer and some STIs among men and female sexual partners of circumcised men

0.85

2.1

0.66

2.1

4.2

1.33

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

South Africa Kenya Uganda

Trial

HIV

In

cid

ence

/100

py

Intervention

Control

Efficacy60% (CI 30-77%)

Efficacy 53% (CI 22-72%)

Efficacy60% (CI 32-76%)

If eight of 10 adult men are circumcised within five years in 14 priority countries in eastern and southern Africa, approximately 3.5 million new HIV infections may be prevented within 15 years, averting as much as $16.5 billion in HIV care and treatment costs.

Almost half of the infections averted are among women

VMMC is provided as a minimum package of services that and is in addition to existing and new HIV prevention interventions

VMMC programs offer unprecedented opportunities to engage men in health education and counseling, notably HTC services

Men who are identified as living with HIV by VMMC programs are referred to the continuum of care, including ART (further decreasing their HIV transmission risk)

Education and Counseling

Screening and treatment for

STIs

Provision of male and female condoms

Safe circumcision procedure

Post op follow up and linkage

to care

Annual number of VMMCs funded through PEPFAR in 14 priority countries

According to WHO and PEPFAR estimates achievement towards the 20 m

• End of 2010 ~3%

• By October 2011 ~5%

• By December 2012 ~ 12% Total=2,352,780

2007-2009 2010 2011 2012

Series1 73200 218900 574200 1486480

100,000

300,000

500,000

700,000

900,000

1,100,000

1,300,000

1,500,000

Chart Title

Nu

mb

er o

f M

Cs

Jhpiego’s Support to Four Countries

2008 2009 2010 2011 20120

50000

100000

150000

200000

250000

300000

350000

400000

16325595

99195

244628

380235

Mozambique, Tanzania, Kenya, Zambia (15-20% of global VMMC)

Commulative

As VMMC is scaled up, challenges faced have differed from country to country

In many populations acceptability is high but demand for services, particularly among ‘older men’ remains low

There is a need for continued innovation both in how VMMC is expanded and in the products and tools that support such expansion, e.g. private sector, increased efficiency and quality of services, new circumcision devices being evaluated by WHO

There is also a need to innovate in the areas of communication, “marketing” and demand generation to maximize the benefits of VMMC for men, women and their families

Sustainability through introduction of Early Infant Male Circumcision

Shang Ring

The Present and Future of the Prevention of Mother-to-Child

Transmission of HIV in Resource-Limited Settings

Rene Ekpini, MD, MPH

JHPIEGO’s PANEL

Washington DC,

 April 25, 2013

1.The present: the Global plan for the Elimination of New HIV Infections among Children by 2015 and Keeping their Alive

2.The Need to Sharpen our Response: why we still need more effective PMTCT programmes

3.The future of PMTCT: reshaping PMTCT programmes and the global agenda

Outline

The present

the Global plan for the Elimination of New HIV

Infections among Children by 2015 and Keeping their

Alive

Global Sub-Saharan Africa

Number of women 15+ living with HIV

15.0 million 8.7 million 58%

Number of pregnant women living with HIV

1.47 million 1.36 million 92%

Number of children <15 years living with HIV

3.3 million 3.1 million 94%

Number of children <15 years newly infected with HIV

330,000 300,000 91%

Number of children <15 years dying of AIDS related causes

230,000 210,000 91%

Global summary of HIV epidemic in women and children, UNAIDS 2011

UNAIDS, Global Report on AIDS, 2012

Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping

Their Mothers Alive (EMTCT)

Source: P.39 of the Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive

Prevention of Mother-to-Transmission of HIV (PMTCT): the four-pronged

approach

Childbearing

women

Women

living

with HIV Pregnant

women

living with

HIV HIV-infected

children

Prevent new

infections Avoid unintended

pregnancies

Prevent

MTCT

Care, treatment and support for mothers & their

children

1

2

3

4

Progress toward MTCT elimination goals in 22 priority countries, 2009-2011

UNAIDS, A progress report on the Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive, 2012

Treatment simplification and optimization for MTCT elimination

1 pill a day for All HIV+ pregnant women

Increasing access for 1000s of women (Coverage & Uptake)

Low transmission rate: Saving life of 1000s of children

Simplification Optimization High impact on maternal

&child health

No CD4 for initiation

TUNISIA

MOROCCO

SAHARA

ALGERIA

MAURITANIA

MALI NIGE

R

LIBYA

CHAD

Mediterranean Sea

Sea

EGYPT

SUDAN

ETHIOPIA

DJIBOUTI

ERITREA

SOMALIAKENYA

TANZANIA

DEMOCRATIC

CENTRAL

RWANDA

GABON

EQUATORIAL

ANGOLA

CONGO

NIGERIA

BENIN

DTVOIRE

SIERRA

SENEGAL

GHANA

THE

GUINEA

LIBERIA

CAMEROON

SOUTH AFRICA

MALAWI

ZAMBIA

MOZAMBIQUE MADAGASCARZIMBABWE

BOTSWANA

SWAZILAND

Indian

Ocean

LESOTHO

NAMIBIA

ANGOLA

Atlantic

Ocean

WESTERN

Red

UGANDA

OF THE CONGO

REPUBLIC

BURUNDI

GUINEAREP. OF

TOGOCOTE

BURKINA

GUINEA

LEONE

GAMBIA

BISSAU

Walvis Bay

SOUTH

REPUBLIC

AFRICAN

THE

AFRICA

Legend Actively implementing or phased roll- out underway

MOH endorsed; preparing for roll-out

Operational planning, piloting, or costing underway

Considering B+

No immediate plans to implement B+

SOUTHSUDAN

Source: PEPFAR PMTCT/Pediatrics TWG - Updated February 28, 2013

Many countries transitioning to lifelong triple ARV regimen for PMTCT (Option

B+)

Note: Haiti is actively implementing Option B+; India is implementing Option B+ in two states

The Need to Sharpen our Response

Why we still need more effective PMTCT

programmes

The performance of the MNCH platform is critical: modalities of MTCT elimination in the US vs

Low- and middle-income countries

Timing of ANC

1st Trim 2nd Trim 3rd Trim

US 73% 21% 5%

LMIC 28% 40% 28%

Pe

rcen

t

Elimination of MTCT requires more than just effective ARV regimens

• Continuing new HIV infections in women of childbearing age in sub-Saharan Africa- HIV prevalence is higher among young women than

young men

- In 2010, 71% of people 15-24 years old living with HIV were women

• HIV incidence in pregnancy in low-resource countries ranges between 1.3-10.7 with an increased risk of HIV transmission to infants during pregnancy and in the postnatal

• High rates of unmet needs for family planning in most countries: women living with HIV have similar or lower rates compared to HIV-uninfected women

Remaining issues with ARV-based interventions

• Even with maternal triple drug regimens, there is still residual postnatal transmission, particularly for infants of women presenting late in pregnancy or in labor

• Actual impact depends on adherence to maternal antiretroviral therapy (ART) especially in the postnatal period

• Even with maternal ART, residual breast milk infection (1-4% at 6 months, 2-6% at 12 months) still exists

The Future of PMTCT

Reshaping PMTCT

programmes and the global agenda

Conceptual framework for a strategic shift for optimal impact

Novel PMTCT-related prevention strategies VACCINES (Pregnant women-Neonates); MICROBICIDES

Targeted interventions for ADOLESCENT GIRLS

Lifelong ART for HIV+ pregnant women

Curing HIV infected

newborns

Integrating HIV testing in FP clinics

Test and Trea

t (ART)

Primary prevention &

ART for sexual partners

1

3

Integrating Family planning in:

ANC & PNC

ART centers/ clinics

Prevention of

unintended

pregnancies

(FAMILY PLANNING

)

Transforming MNCH services for effective delivery of an integrated

model of care

Early ANC booking during 1st trimester

Focused ANC

(at least 4 visits)

Institutional delivery

Postnatal care

Triple ARVs for PMTCT

Infant feeding counselling and support

Facility and community level interventions

Removing supply and demand side bottlenecks

Retention in care and treatment

Challenges ahead -1

•Scaling up “test and treat” approach in low prevalence and concentrated epidemic settings: what approaches for HIV testing and counseling?

•Rethinking the public health and clinical purpose of CD4 counts (vs low cost point of care viral load) and Early Infant Diagnosis (DBS/PCR) in a well performing programme

At the programmatic level

Challenges ahead -2

• Mainstreaming MTCT elimination in the global health agenda and national development strategies for a broader impact beyond HIV

• Do not forget HIV-infected children: influencing the global agenda and national responses for paediatric HIV treatment and care in the context of MTCT elimination

• Creating a social movement to improve accountability: establishing durable community accountability mechanisms that involve women and men living with HIV

At the policy level

Two Worlds, Two Realities, One Hope: addressing inequity for social justice

Special thanks to: Lynne Mofenson

The Present & Future of HIV Prevention

An Advocate’s Perspective

Mitchell WarrenExecutive Director, AVAC25 April 2013

“Few could have imagined that we’d be talking about the real possibility of an AIDS-free generation. But that’s what we’re talking about.”

December 1, 2011

“An AIDS free generation is within our reach.” February 12, 2013

AIDS-free generation

Cure

Ending AIDS

Ending the epidemic

Functional cure

Preventive vaccine

Treatment as prevention

Therapeutic vaccine

“Epidemic” is occurrence of more cases of disease than would normally be expected in a specific place or community over a period of time. “Ending” would lower rate of new infections, and even eliminate new cases in some populations. See also “beginning to end…”

Sometimes used in reference to the specific goal of eliminating new pediatric infections by 2015, allowing a generation of children to be born without HIV.

Strategy to eliminate HIV from a person’s body. A cure would be a revolutionary breakthrough, but is not a requisite for ending the epidemic.

HIV is the virus that causes the syndrome of diseases known as AIDS. A goal of “ending AIDS” can be understood as effectively treating all people with HIV and ensuring them long, healthy lives.

Strategy to suppress HIV viral load keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled.

Vaccine used in HIV-negative individuals to prevent or dramatically reduce the risk of infection. Many believe that the long-term goal of ending the epidemic—and preventing a surge of new infections—depends on a vaccine.

Vaccine designed to stimulate the immune response to HIV in a person already infected with the virus, in order to control the infection. Also referred to as an immunotherapeutic vaccine.

Systemtic use of ART to reduce sexual transmission risk in HIV-positive people. Also known as TasP, T4P, TisP and TLC+ (testing, linkage to care plus tx).

Mind the Language

Prevention Paradigm 2013 and beyondDifferent Strokes for Different Folks

Method Contraception HIV Prevention

Behaviour ✓ ✓

Barrier Methods ✓ ✓

Gels ✓

Rings ✓

Oral pill ✓ ✓

Injectables ✓

Implants ✓

Surgical procedures ✓ ✓

Treatment ✓

CO

MB

IN

E

Demonstrate proven tools for immediate impact

• Daily oral TDF/FTC as PrEP• 1% tenofovir gel

Develop long-term solutions to end the epidemic• AIDS vaccines• Cure• Multi-purpose prevention technologies• Next generation ARV-based prevention• Non-ARV-based microbicides• Rectal microbicides

Years to Impact Zero to 5 5 to 10 10 to End

GOAL: A sustained d e c l i n e i n H I V infections (now at 2.5 million/year)

• Define and initiate the “core package” of PrEP demonstration projects

• Safeguard HIV Prevention Research Funding

• End confusion about “combination prevention”

• Narrow gaps in treatment cascade• Prepare for new non-surgical male

circumcision devices

• Testing• Treatment• Voluntary Medical Male Circumcision • Female and male condoms• Prevention of pediatric infection• Syringe exchange programs

Deliver proven tools for immediate impact

AVAC Report 2012: Achieving the End – One year and counting. www.avac.org/report2012.

Three-Part Agenda for Ending AIDS

DNA/

Ad5

2010 2011 2012 2013 2014 2015 2016

1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4

Positive efficacy result

No effect

Regulatory submission/filing

Planned

Final results pending

DPV ring

Oral TDF/FTC

Oral TDF

Rectal TFV gel

TFV gel

TMC278 LA Injectable

DNA/Ad5

TIMELINE LEGEND

Pox-Protein

HIV Prevention Options Timeline * **

* Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/pxrd. ** Not all trials included are effectiveness trials. Trials included on this list are mainly phase II/IIb, III/IIIb and IV trials.

Bangkok Tenofovir Study/CDC 4370

Partners PrEP Partners PrEP (no placebo)2008

2005

2009 VOICE/MTN 003

Ora

l TDF

/FTC

Ora

l TDF

iPrEx2007 iPrEx Open-Label Extension (OLE)

2009 FEM-PrEP

US FDA approval

CAPRISA 0042007

2007 TDF2 Open-Label ExtensionTDF2/CDC 4940

TFV

gel

FACTS 001Earliest regulatory submission

VOICE/MTN 0032009

MTN 017 Rect

al

TFV

gel

DPV

Ring The Ring Study/IPM 027

ASPIRE/MTN 020

Earliest regulatory submission

Possible Long-Acting Injectable efficacy

TMC

278

LA In

ject

.Po

x-Pr

otei

n

Various Phase I/II preliminary and bridging studiesRV 1442004

South Africa Licensure

South Africa Research

Thai Licensure

2009 HVTN 505

Additional demonstration projects & intermittent PrEP studies

CAPRISA 008

FACTS 002 and other adolescent studies

Various Phases of Long-Acting Injectables (TMC278, GSK744)

AVAC Report 2012: Achieving the End – One year and counting. www.avac.org/report2012

AVAC, April 2013

Who is actually in the trial?

Trial Median Age

Married/Stable partner Efficacy Adherence

(as per drug levels)

CAP 004 24 88% TFV gel: 39% [CI = 6-60%] 50.5%

iPrEx 27 Oral TDF/FTC: 42% [CI = 18-60%] 51%

Partners PrEP 36 98% Oral TDF: 67% [CI = 44-81%]

Oral TFD/FTC: 75% [CI = 55-87%] 83%81%

TDF-2 25 6% Oral TDF/FTC: 62% [CI = 22-83%] 80.5%

FEM-PrEP 24 31% Oral TDF/FTC: No Protection 24%

VOICE 25 21%TFV gel: No protectionOral TDF: No protectionOral TDF/FTC: No protection

23%28%29%

VOICE-SA 25 8% To come

VOICE-Ug 28 50% To come

VOICE-Zim 28 94% To come

FACTS 2015

The most recent bottom line(s)

Prevention research is hard – and unpredictable!We need to improve adherence

By improving adherence supportBy “improving” existing products through marketingBy developing other types of products

We need to better understand behaviours – sexual, product use, trial participation and personal reporting

…and the “pre-behaviours” – risk perception